Trinucleotide repeat (TNR) expansions cause at least 15 neurodegenerative disorders, including Huntington's disease (HD), Friedreich ataxia, myotonic dystrophy and >90% of inherited spinocerebellar ataxias (SCAs). While these diseases are devastating and relentlessly fatal, they show several fascinating genetic properties. First, these mutations occur at a much higher frequency that spontaneous mutations, in some extreme cases with a frequency approaching 100%. Also, TNR expansions are a unique form of mutation in which repeating triplets of nucleotides linearly amplify themselves between successive generations. Amplification of the repeating sequence also produces genetic anticipation, a worsening of disease phenotype of the TNR diseases. I will use a sensitive, specific and portable genetic assay recently optimized in the laboratory of Dr. Robert Lahue to investigate the etiology of TNR instability in human cells. This work will not only enable me to receive expert training in an interesting and important area of basic science research, but will also allow me to advance our understanding of an entire class of fatal neurological diseases. [unreadable] [unreadable]